60668-26-0Relevant articles and documents
Use of the dehydrophos biosynthetic enzymes to prepare antimicrobial analogs of alaphosphin
Bougioukou, Despina J.,Ting, Chi P.,Peck, Spencer C.,Mukherjee, Subha,Van Der Donk, Wilfred A.
supporting information, p. 822 - 829 (2019/01/30)
The C-terminal domain of the dehydrophos biosynthetic enzyme DhpH (DhpH-C) catalyzes the condensation of Leu-tRNALeu with (R)-1-aminoethylphosphonate, the aminophosphonate analog of alanine called Ala(P). The product of this reaction, Leu-Ala(P), is a phosphonodipeptide, a class of compounds that have previously been investigated for use as clinical antibiotics. In this study, we show that DhpH-C is highly substrate tolerant and can condense various aminophosphonates (Gly(P), Ser(P), Val(P), 1-amino-propylphosphonate, and phenylglycine(P)) to Leu. Moreover, the enzyme is also tolerant with respect to the amino acid attached to tRNALeu. Using a mutant of leucyl tRNA synthetase that is deficient in its proofreading ability allowed the preparation of a series of aminoacyl-tRNALeu derivatives (Ile, Ala, Val, Met, norvaline, and norleucine). DhpH-C accepted these aminoacyl-tRNA derivatives and condensed the amino acid with l-Ala(P) to form the corresponding phosphonodipeptides. A subset of these peptides displayed antimicrobial activities demonstrating that the enzyme is a versatile biocatalyst for the preparation of antimicrobial peptides. We also investigated another enzyme from the dehydrophos biosynthetic pathway, the 2-oxoglutarate dependent enzyme DhpA. This enzyme oxidizes 2-hydroxyethylphosphonate to 1,2-dihydroxyethylphosphonate en route to l-Ala(P), but longer incubation results in overoxidation to 1-oxo-2-hydroxyethylphosphonate. This α-ketophosphonate was converted by the pyridoxal phosphate dependent enzyme DhpD into l-Ser(P). Thus, the dehydrophos biosynthetic enzymes can generate not only l-Ala(P) but also l-Ser(P).
CONVERSION OF AMINO ACIDS AND DIPEPTIDES INTO THEIR PHOSPHONIC ANALOGS; Aminoalkylphosphonic acids and peptides II.
Oesapay, George,Szilagyi, Ildiko,Seres, Jenoe
, p. 2977 - 2984 (2007/10/02)
Acylamino carboxylic acids were degradated by the Hunsdiecker-reaction; the bromo-derivatives were reacted with NaPO(OC2H5)2.Aminophosphonic acids were obtained by acidic hydrolysis, and half-blocked derivatives by the selective removal of masking substituents.Two phosphonopeptides were also prepared by this route.
Chemical process for the production of α-aminophosphonic acids and peptide derivatives
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, (2008/06/13)
The present invention provides a process for the production of physiologically-useful α-aminophosphonic acids and peptide derivatives of the formula: STR1 wherein R and R1 may be the same or different and each can be hydrogen, deuterium or an optionally substituted lower alkyl group, lower alkenyl, lower alkynyl, cycloalkyl, aryl or heterocyclic radical containing one or more oxygen, nitrogen or sulphur atoms and which may be fused to an aromatic ring, a lower alkyl group substituted by a cycloalkyl radical, a lower alkyl group substituted by an aryl radical, a lower alkyl group substituted by a heterocyclic radical as defined above or R and R1 together form a polymethylene chain optionally interrupted by an oxygen, nitrogen or sulphur atom, or R1 represents, together with the C(R)--N2 can be hydrogen, optionally substituted lower alkyl, cycloalkyl, aryl or lower alkyl substituted by a cycloalkyl radical, lower alkyl substituted by a heterocyclic radical containing one or more nitrogen atoms; by a heterocyclic radical containing one or more nitrogen atoms, or R2 together with the C(H)--N residue to which it is attached, may represent the atoms required to complete a heterocyclic radical; and n is 0, 1, 2, 3 or 4; comprising oxidizing, using an oxidizing agent, a compound having the formula: STR2 wherein R, R1, R2 and n have their previous significance, and Z is H or a protecting group usually used for an amino group; and then removing any protecting group.
